Basics
Description
Neonatal alloimmune thrombocytopenia (NAIT) is one of the major causes of severe thrombocytopenia in the newborn. é á
- Analogous to ABO/Rh incompatibility but involves platelets instead of RBCs
- Presents with bleeding complications including petechiae, bruising, mucosal bleeding, and/or intracranial hemorrhage (ICH) that can occur in utero
Epidemiology
- Incidence is ó ł ╝1:1,000 to 1:2,000 live births.
General Prevention
The disease cannot be prevented. é á
Pathophysiology
Antibody-mediated platelet destruction é á
Etiology
Maternal IgG antibodies (Ab), directed against paternally inherited platelet-specific antigens in the fetus, cross the placenta, enter the fetal circulation, and attack fetal platelets. é á
- HPA-1a (formerly PLA-1) incompatibility is by far the most common cause of NAIT in those of Caucasian ancestry, accounting for ó ł ╝75% of cases. The disease happens when the mother is HPA-1a negative (HPA 1b/1b) and father is HPA-1a positive (HPA 1a/1a or 1a/1b). If the fetus inherits HPA-1a from father, maternal exposure to HPA-1a " ôpositive fetal platelets during pregnancy causes mother to generate anti " ôHPA-1a IgG Ab. Anti " ôHPA-1a Ab crosses the placenta and causes platelet destruction.
- Other common antigens implicated in NAIT include HPA-2, HPA-3, HPA-5, HPA-9, and HPA-15.
- HPA-4 incompatibility accounts for the majority of cases in Asian populations.
- At least 23 other low-frequency antigens have been reported in a small fraction of cases.
- HPA-1a " ônegative mothers who are HLA-DRB3*0101 positive are far more likely to develop Ab than those who are DRB3 negative.
- The role of HLA platelet antigens in NAIT is unclear.
Diagnosis
History
- NAIT is suspected in a non " ôill-appearing neonate who presents shortly after birth with clinical signs of bleeding and documented thrombocytopenia.
- Maternal history of previous births with thrombocytopenia, NAIT, ICH, or fetal losses?
- Maternal history of thrombocytopenia or ITP?
- Is current maternal platelet count normal?
- Family history of thrombocytopenia or bleeding disorders?
- Symptoms suggestive of an infection in the mother or infant?
- Medications used during pregnancy or in the newborn period
Alert
Maternal platelet count in NAIT should be normal. Thrombocytopenia in the mother, and/or a history of maternal ITP should prompt you to consider alternative diagnoses such as autoimmune thrombocytopenia (i.e., antibodies directed toward maternal platelets, passively transfer into the fetal circulation, and destroy fetal platelets). é á
Physical Exam
- Most neonates with NAIT are well and nonseptic appearing.
- May have mild easy bruising and bleeding symptoms
- If severely affected, may develop ICH
- Document the following exam findings:
- General: Evaluate for evidence of a congenital disorder (e.g., dysmorphic features).
- Head/neck: Exclude presence of full fontanelle and cephalohematoma.
- Abdomen: Exclude presence of organomegaly and mass.
- Extremities: Exclude presence of radial-thumb defects.
- Neurologic exam: Evaluate for irritability, lethargy, seizure, and focal neurologic deficits.
- Skin: Evaluate for pallor, petechiae, ecchymoses, hemangiomas, and vascular lesions. Evaluate for bleeding from phlebotomy sites, heel sticks, circumcision, and the umbilical cord.
- If congenital anomalies, hepatosplenomegaly, abdominal mass, or skeletal defects are present, consider alternative diagnoses.
Diagnostic Tests & Interpretation
Lab
- CBC
- Isolated thrombocytopenia: Platelets are often <50,000/ Ä ╝L at birth.
- May see anemia if the infant has suffered severe bleeding complications
- Screening coagulation studies
- PT, PTT, thrombin time, and fibrinogen should be normal.
- Maternal platelet count: should be normal
- NAIT testing: HPA incompatibility between mother and child needs to be identified. Testing can be performed on mother and father to avoid collecting blood samples on the infant.
- Serologic testing: Maternal serum containing platelet-reactive antibodies is tested against a panel of platelet glycoproteins, including HPA-1a, to look for incompatibility.
- Platelet cross-matching: Maternal serum containing platelet-reactive antibodies is tested against washed paternal platelets to look for incompatibility.
- Testing also against washed maternal platelets can exclude "autoantibodies " Ł as seen in ITP.
- Platelet antigen genotyping: DNA-based testing of the platelet glycoprotein genotype of both parents can be performed in only a few laboratories but can reveal potential incompatibilities (i.e., specifically HPA-1 through HPA-6, HPA-9, and HPA-15).
Imaging
Head ultrasound to rule out ICH é á
Differential Diagnosis
- Infection
- Bacterial or viral (e.g., rubella, cytomegalovirus)
- Congenital
- Thrombocytopenia absent radius
- Amegakaryocytic thrombocytopenia
- Wiskott-Aldrich syndrome: X-linked condition with triad of immunodeficiency, eczema, and thrombocytopenia (small platelet size)
- May-Heglin anomaly: D â Âhle bodies in WBCs (large platelet size)
- Immunologic
- Autoimmune thrombocytopenia (i.e., maternal ITP): The degree of thrombocytopenia in autoimmune thrombocytopenia tends to be much less severe than in NAIT.
- Hematologic
- DIC: increased platelet consumption (e.g., sepsis, NEC)
- Thrombosis: for example, renal vein thrombosis, catheter-associated thrombosis
- Hemangioma with Kasabach-Merritt syndrome
- Oncologic
- Leukemia
- Neuroblastoma
- Down syndrome " öTMD
- Metabolic
- Methylmalonic acidemia
- Isovaleric acidemia
Treatment
General Measures
- Daily platelet counts should be obtained until there is documentation of improvement without treatment/intervention.
- Close monitoring for any evidence of bleeding complications, especially ICH
- Avoidance of any invasive procedures (e.g., arterial or lumbar punctures) until platelet count is in a more stable range.
- Platelet count <30,000/ Ä ╝L is generally accepted as a threshold for therapeutic intervention. Much higher thresholds are used if ICH is present.
- Treatment is platelet transfusion (10 mL/kg).
- Potential sources of platelets for transfusion
- HPA-1b/1b (i.e., HPA-1a neg) platelets
- An excellent 1st choice but not always readily available
- It is not appropriate to await HPA-matched platelets for transfusion, especially if the infant has clinically significant bleeding.
- Random donor platelets
- Most readily available but not ideal, given that 98% of the population is HPA-1a positive.
- Will usually elevate the platelet count transiently until a more suitable blood product can be obtained
- Maternal apheresis platelets
- Ideal source for platelets but can take days to obtain
- Do not wait for maternal platelets if the infant has clinically significant bleeding.
- Important: Maternal platelets must be washed or volume reduced to remove antibody-containing maternal plasma.
- Failure to wash or volume reduce maternal platelets may result in prolongation of the fetal thrombocytopenia.
- HPA-specific platelets
- If an incompatibility other than HPA-1a is identified, consult your blood bank to see if HPA-specific platelets are available.
- IVIG is another potential therapeutic agent.
- May be used concurrently with platelet transfusions when the platelet count is <30,000/ Ä ╝L, especially when clinical signs of bleeding are present.
- Consider use as monotherapy when the platelet count is <30,000 " ô50,000/ Ä ╝L. Dose of IVIG is 1 g/kg. Multiple doses may be required.
Alert
All blood products administered should be treated appropriately for a neonate, that is, irradiated, CMV negative, ABO compatible, volume reduced, or washed if indicated. é á
Ongoing Care
Follow-up Recommendations
- Given the implications for future pregnancies, NAIT testing should be considered in all infants with thrombocytopenia (<50,000/ Ä ╝L), even if there is another likely etiology.
- If diagnosis of NAIT is confirmed, family counseling regarding management of future pregnancies is strongly recommended. Consultation with a high-risk obstetrician and perinatologist should be made for any future pregnancy at risk for NAIT.
Prognosis
- Overall prognosis is fair to good. Most patients will experience little morbidity or mortality. ICH may lead to very significant morbidity and/or mortality.
- Most cases will resolve in 1 " ô4 weeks.
Complications
- ICH: incidence ó ł ╝20%, most occur antenatal
- Bleeding from umbilical stump, phlebotomy sites, and/or circumcision
- Petechiae and ecchymoses
- Cephalohematoma
- GI or GU bleeding
Additional Reading
- Bussel é áJB, Primiani é áA. Fetal and neonatal alloimmune thrombocytopenia: progress and ongoing debates. Blood Rev. 2008;22(1):33 " ô52. é á[View Abstract]
- Peterson é áJA. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol. 2013;161(1):3 " ô14. é á[View Abstract]
- Symington é áA, Paes é áB. Fetal and neonatal alloimmune thrombocytopenia: harvesting the evidence to develop a clinical approach to management. Am J Perinatol. 2011;28(2):137 " ô144. é á[View Abstract]
Codes
ICD09
- 776.1 Transient neonatal thrombocytopenia
- 287.33 Congenital and hereditary thrombocytopenic purpura
ICD10
- P61.0 Transient neonatal thrombocytopenia
- D69.42 Congenital and hereditary thrombocytopenia purpura
SNOMED
- 240305000 neonatal thrombocytopenia due to platelet alloimmunization (disorder)
- 234482009 Amegakaryocytic thrombocytopenia (disorder)
FAQ
- Q: Can an infant with NAIT safely receive maternal breast milk?
- A: Colostrum and maternal breast milk (MBM) contain immunoglobulins that are passively transferred to an infant. In a pregnancy affected by NAIT, this may include antiplatelet antibodies. The amount of antiplatelet antibodies transferred in MBM is probably minor and there are no reports of adverse consequences in infants with NAIT who have received MBM. The use of MBM in infants with NAIT therefore appears to be safe and should not be discouraged.
- Q: What is the HPA-1a " ônegative (homozygous HPA-1b/1b) mother 's risk of having other affected newborns?
- A: It depends on the genotype of the father.
- If the father is homozygous for HPA-1a (HPA 1a/1a), all offspring will be heterozygous HPA 1a/1b positive and at great risk for developing NAIT.
- If the father is heterozygous for HPA-1a (HPA 1a/1b), 50% of offspring will be at risk for developing NAIT.
- Q: Can NAIT happen in a 1st pregnancy?
- A: Unlike hemolytic disease of the newborn due to Rh incompatibility, NAIT can occur even in 1st born offspring. It is important to know that NAIT tends to become more severe with each subsequently affected pregnancy.